2759 - Identification of Biomarkers for Post-Treatment Cardiotoxicity in Mediastinal Lymphoma Patients
Presenter(s)
I. Iamundo De Cumis1, M. A. Deidda1, R. F. Farigu2, M. Congiu2, G. Fadda1, S. Piras2, S. Cossa2, P. Manca2, M. P. Simula2, S. V. Usai2, D. Dessì2, S. Oppi2, A. Meloni3, S. Zucca2, G. Caocci2, C. Marinelli2, P. Siotto2, A. Squassina3, and R. Barbara2,4; 1ARNAS BROTZU, CAGLIARI, Italy, 2ARNAS BROTZU, Cagliari, Italy, 3University of Cagliari, Cagliari, Italy, 4ospedale brotzu, Cagliari, Sardegna, Italy
Purpose/Objective(s):
To investigate molecular biomarkers and functional cardiac alteration associated with early cardiotoxicity in patients (pts) with mediastinal lymphoma treated with chemotherapy (CT) and radiation therapy (RT)
Materials/Methods:
From August 2023 to September 2024, 10 pts were enrolled (4 with Primary Mediastinal B-cell Lymphoma, and 6 with bulky Stage II mediastinal Hodgkin Lymphoma). All received CT followed by Involved Site RT via IMRT (total dose 30–36 Gy).
Molecular and instrumental monitoring was performed at 4 time points: T0 (Baseline), T1 (48h after-CT), T2 (48h after RT), and T3 (6 months post RT). Biomarkers included B-type natriuretic peptide (BNP), high sensibility Troponin (hs-Tn) and 8 cardiac-specific microRNAs (miRNA). Instrumental evaluations included: Cardiac Computed Tomography Angiography (CCTA) and Cardiac Magnetic Resonance Imaging (MRI) at T0, and echocardiogram (ETG) with 2D global longitudinal strain (2D-GLS) at each time-point. CCTA and MRI images were fused with simulation CT scan and cardiac substructures were contoured: Whole Heart (WH), chambers, coronary arteries, valves, and the interventricular septum (IVS). Cardiac events (CE) were defined as any subclinical alteration identified by ETG
Results:
At each time point, pts underwent an evaluation of blood BNP, hs-Tn, and miRNAs, and 2D-GLS ETG to correlate biomarkers with cardiac function. miRNAs expression was quantified using TaqMan microRNA Assays. Subclinical CEs were identified in 4/10 pts, mainly based on GLS reduction (>15% relative decrease): Three patients showed GLS decline at T1 and/or T2, and ETG confirmed IVS hypokinesia in all of them. One additional patient showed localized IVS akinesia despite stable GLS.
In the entire sample, mean GLS worsened after CT and RT, with a trend toward recovery at follow-up. Mean hs-Tn increased from baseline (2.9 ng/L) to T1 (19 ng/L) and T2 (14.7 ng/L), then decreased at T3 (6.6 ng/L). Mean BNP was 27.8 pg/mL at T0, decreased at T1 (21.9 pg/mL), and increased at T2 (26.4 pg/mL) and T3 (37.3 pg/mL).
Mean dose (MD) to the WH, left ventricular (LV), IVS and LV lateral wall were 5.12, 2.4, 2.27 and 1.74 Gy respectively. Of the 8 selected miRNAs, only miR-133, miR-145, miR-21 and miR-33 were successfully detected. Baseline BNP, GLS, hs-Tn, and cardiac mean doses were not predictive of CEs. In contrast, lower baseline miR-21 was predictive of CEs (p=0.004)
Given the limited sample size, longitudinal analysis was restricted to the comparison between T0 and T3. Changes in miR-21 correlated with changes in BNP (p<0.001), and both were significantly associated with the CEs occurrence (p=0.037), with pts experiencing CEs showing increases in both markers over time
Conclusion: